-
The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2021A recent serologic study and reports of increased serum total IgE (IgE-t) and eosinophil counts have suggested that the prevalence of atopy is more common in patients...
INTRODUCTION
A recent serologic study and reports of increased serum total IgE (IgE-t) and eosinophil counts have suggested that the prevalence of atopy is more common in patients with mycosis fungoides (MF) than previously recognized.
PATIENTS AND METHODS
Patients with clinicopathologic features that were diagnostic and/or consistent with MF and/or the presence or absence of an atopic disorder (eg, allergic rhinitis, asthma, eczematous dermatitis), which was determined by patient history, eosinophil counts, and serum IgE-t obtained at evaluation, were selected from a patient registry. The MF population was divided into those with atypical and typical clinical presentations. We performed matching of controls using age, sex, and race from the 2005 to 2006 National Health Education Survey.
RESULTS
A history of allergic rhinitis was recorded for 186 of 728 patients (25.5%) with typical MF and 71 of 229 patients (31%) with atypical MF. However, the prevalence of asthma and eczema was low. The IgE-t and eosinophil counts were higher for patients with typical MF than for controls and for patients with atopic diathesis than for patients without atopy. The IgE-t and eosinophil counts were higher for the patients with advanced-stage MF compared with those for the patients with less-advanced disease for both atopic and nonatopic cohorts. In the Cox model with age and clinical stage as covariates, a history of atopy, increased IgE-t, and blood eosinophilia (> 500 cells/mm3) did not correlate with overall survival.
CONCLUSION
The findings from the present study did not reveal a significant association of atopy in patients with MF. However, atopy is a factor in the increased IgE-t and eosinophil counts observed in MF. Another factor is related to the disease stage, including possibly the influence of cytokines secreted by T-helper type 2-polarized neoplastic cells.
Topics: Adult; Aged; Asthma; Dermatitis, Atopic; Eosinophils; Female; Humans; Immunoglobulin E; Leukocyte Count; Male; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Prevalence; Registries; Retrospective Studies; Rhinitis, Allergic; Risk Factors; Severity of Illness Index; Skin Neoplasms; Survival Rate
PubMed: 33342729
DOI: 10.1016/j.clml.2020.11.007 -
Dermatology (Basel, Switzerland) 2020Poikilodermatous mycosis fungoides (pMF) is characterized by poikiloderma areas, typically involving the major flexural areas and trunk. Its presentation can be... (Comparative Study)
Comparative Study
BACKGROUND
Poikilodermatous mycosis fungoides (pMF) is characterized by poikiloderma areas, typically involving the major flexural areas and trunk. Its presentation can be generalized or admixed with other forms of MF. Previous studies fail to correlate the clinical presentation with prognosis and laboratory findings. Some reports show pityriasis lichenoides chronica (PLC) preceding the poikiloderma.
OBJECTIVES
Correlate prognostic, histopathological and molecular aspects of pMF with its clinical presentation.
METHODS
Retrospective analysis of 14 cases of generalized pMF (GpMF), 22 of localized pMF (LpMF) and 17 of pMF admixed with other forms of MF (mix-pMF).
RESULTS
Female predominance and lower age at diagnosis was found in all groups compared to classic MF, a high prevalence of PLC-like lesions in the GpMF group and a high rate of hypopigmented lesions in the mix-pMF group. There were 2 deaths within the GpMF group. Histology was similar to previously reported findings, as was the prevalence of CD4 T-cell infiltrate, compared to CD8. The T-cell clonality positivity was lower in the GpMF group, compared to other groups (27% GpMF, 80% LpMF and 100% mix-pMF).
DISCUSSION
This is the first article to categorize the different forms of pMF and correlate them with clinical and laboratory findings. The dermatological presentation differs among the groups. There was a high frequency of PLC-like lesions within the GpMF group and of hypopigmented lesions in mix-pMF. The histological and immunohistochemical findings were similar to those previously reported. Aggressive treatments are not recommended due to the good prognosis of all pMF forms. The low positivity of T-cell clonality in the GpMF group should be investigated.
Topics: Clone Cells; Female; Humans; Immunohistochemistry; Male; Middle Aged; Mycosis Fungoides; Parapsoriasis; Prognosis; Retrospective Studies; Skin Neoplasms; T-Lymphocytes
PubMed: 31550709
DOI: 10.1159/000502027 -
Dermatology (Basel, Switzerland) 2021Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), is a lymphoproliferative disorder characterized by proliferation of malignant T cells...
BACKGROUND
Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL), is a lymphoproliferative disorder characterized by proliferation of malignant T cells in a chronic inflammatory environment in the skin. The nature of MF is still not fully understood, but aberrant microRNA (miR) expression and function seem to play an important role in the pathogenesis and disease progression and have been proposed as a putative disease marker. Recent studies have reported aberrant expression of miR-93 in situin MF lesions and linked dysregulated miR-93 expression to advanced stages of MF. However, the pathophysiological role of miR-93 in MF is unknown.
OBJECTIVE
Here, we provide the first evidence that miR-93 targets the cell cycle regulator cyclin-dependent kinase inhibitor p21 and promotes growth of malignant T cells in MF.
METHODS/RESULTS
Thus, inhibition of miR-93 in MF patient-derived malignant T-cell lines increases expression of p21 and inhibition of malignant proliferation. Notably, treatment with the histone deacetylase inhibitor Vorinostat (SAHA) reduces miR-93 expression and enhances p21 expression in the malignant T cells. Importantly, transfection with an miR-93 mimic partly blocks SAHA-induced p21 expression.
CONCLUSIONS
we provide evidence that enhanced expression of the putative oncogenic miR, miR-93, represses the cell cycle inhibitor p21 and promotes proliferation of malignant T cells. Moreover, we demonstrate that SAHA triggers p21 expression - at least partly - through an inhibition of miR-93.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Gene Expression; Histone Deacetylase Inhibitors; Humans; MicroRNAs; Mycosis Fungoides; RNA, Messenger; Skin Neoplasms; Vorinostat
PubMed: 32335549
DOI: 10.1159/000505743 -
Cells Jul 2023Mycosis fungoides (MF) is the most common cutaneous lymphoma characterized by an indolent course. Prognosis is stage-based but this approach does not reflect the...
Mycosis fungoides (MF) is the most common cutaneous lymphoma characterized by an indolent course. Prognosis is stage-based but this approach does not reflect the different outcomes within stages. Considering that tumor microenvironment is known to be involved in MF pathogenesis and progression, we decided to investigate 99 MF cases by using the PanCancer Immune Profiling Panel. We identified and validated a signature of 9 genes able to predict MF survival and distinguish a high-risk group with a worse outcome from a low-risk group of cases with a better outcome. At the molecular level, low-risk vs. high-risk cases reported a global upregulation of immune genes, enriched in cytokines, and a higher density of dendritic cells and mast cells, possibly associated with a more favorable clinical course.
Topics: Humans; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms; Risk Factors; Lymphoma, Non-Hodgkin; Tumor Microenvironment
PubMed: 37566023
DOI: 10.3390/cells12151944 -
Best Practice & Research. Clinical... Mar 2023Cutaneous lymphomas and lymphoid proliferations (LPD) in children, adolescents, and young adults (CAYA) are a heterogeneous group of lymphoid neoplasms that present... (Review)
Review
Cutaneous lymphomas and lymphoid proliferations (LPD) in children, adolescents, and young adults (CAYA) are a heterogeneous group of lymphoid neoplasms that present formidable diagnostic challenges to clinicians and pathologists alike. Although rare overall, cutaneous lymphomas/LPD occur in real-world settings and awareness of the differential diagnosis, potential complications, and various therapeutic approaches will help ensure the optimal diagnostic work-up and clinical management. Lymphomas/LPD involving the skin can occur as primary cutaneous disease in a patient that characteristically has lymphoma/LPD confined to the skin, or as secondary involvement in patients with systemic disease. This review will comprehensively summarize both primary cutaneous lymphomas/LPD that occur in the CAYA population as well as those CAYA systemic lymphomas/LPD with propensity for secondary cutaneous involvement. Focus on the most common primary entities occurring in CAYA will include lymphomatoid papulosis, primary cutaneous anaplastic large cell lymphoma, mycosis fungoides, subcutaneous panniculitis-like T-cell lymphoma, and hydroa vacciniforme lymphoproliferative disorder.
Topics: Young Adult; Humans; Child; Adolescent; Skin Neoplasms; Lymphomatoid Papulosis; Mycosis Fungoides; Diagnosis, Differential
PubMed: 36907638
DOI: 10.1016/j.beha.2023.101448 -
International Journal of Molecular... Apr 2023Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL) and is characterized by epidermotrophism of malignant CD4+ T-lymphocytes. When MF...
Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL) and is characterized by epidermotrophism of malignant CD4+ T-lymphocytes. When MF advances to a recurrent stage, patients require treatment with systemic therapies such as vorinostat, a histone deacetylase inhibitor. While vorinostat has been shown to exhibit anti-tumor activity in MF, its exact molecular mechanism has yet to be fully discerned. In the present study, we examined the transcriptomic and proteomic profiles of vorinostat treatment in two MF cell lines, Myla 2059 and HH. We find that vorinostat downregulates CTLA-4, CXCR4, and CCR7 in both cell lines, but its effect on several key pathways differs between the two MF cell lines. For example, vorinostat upregulates CCL5, CCR5, and CXCL10 expression in Myla cells but downregulates CCL5 and CXCL10 expression in HH cells. Furthermore, vorinostat upregulates IFN-γ and IL-23 signaling and downregulates IL-6, IL-7, and IL-15 signaling in Myla cells but does not affect these pathways in HH cells. Although Myla and HH represent established MF cell lines, their distinct tumor origin from separate patients demonstrates that inherent phenotypic variations within the disease persist, underscoring the importance of using a variety of MF cells in the preclinical development of MF therapeutics.
Topics: Humans; Vorinostat; Proteomics; Mycosis Fungoides; Lymphoma, T-Cell, Cutaneous; Skin Neoplasms
PubMed: 37175780
DOI: 10.3390/ijms24098075 -
Journal of the European Academy of... Jun 2020Psoriasis has been controversially associated with risk of non-Hodgkin lymphoma (NHL) and mycosis fungoides (MF). Also patients who developed MF after systemic treatment... (Review)
Review
Psoriasis has been controversially associated with risk of non-Hodgkin lymphoma (NHL) and mycosis fungoides (MF). Also patients who developed MF after systemic treatment for psoriasis have been reported, and some authors suggested that the association between MF and psoriasis is not infrequent. We performed an extensive literature review in order to examine the risk of developing MF in psoriatic patients with a systematic search of the English-language databases. An increased risk for lymphoma overall in psoriatic patients has been found only by three out of seven studies. The risk of developing MF in psoriatic patients has been investigated by different studies in different populations and with different methodologies presenting bias and limitations, and it seems reasonable that misclassification between psoriasis and MF may explain the association reported. In contrast to the large number of psoriatic patients treated with biologicals, only 27 case reports of MF after biological therapy for psoriasis have been reported, and in 10 cases, the initial psoriasis diagnoses were then revised as MF. A true association between MF and psoriasis is possible, but the real incidence and prevalence are still unknown. The reported higher risk of developing MF in psoriatic patients should be reconsidered in the light of the bias of misclassification and the low magnitude reported in previous studies. There is not enough evidence to support a causal relation among biological therapies and MF in psoriatic patients.
Topics: Biological Products; Diagnostic Errors; Humans; Mycosis Fungoides; Psoriasis; Risk Factors; Skin Neoplasms
PubMed: 31856345
DOI: 10.1111/jdv.16160 -
F1000Research 2020Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of extranodal non-Hodgkin lymphomas involving primarily the skin and mycosis fungoides is its most... (Review)
Review
Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of extranodal non-Hodgkin lymphomas involving primarily the skin and mycosis fungoides is its most frequent entity. Whereas most patients show an indolent course in early disease (clinical stages IA to IIA), some patients progress to advanced disease (stage IIB or higher), and the 5-year survival rate is unfavorable: only 47% (stage IIB) to 18% (stage IVB). Except for allogeneic stem cell transplantation, there is currently no cure for CTCL and thus treatment approaches are palliative, focusing on patients' health-related quality of life. Our aims were to review the current understanding of the pathogenesis of CTCL, such as the shift in overall immune skewing with progressive disease and the challenges of making a timely diagnosis in early-stage disease because of the lack of reliable positive markers for routine diagnostics, and to discuss established and potential treatment modalities such as immunotherapy and novel targeted therapeutics.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Quality of Life; Sezary Syndrome; Skin Neoplasms
PubMed: 32419924
DOI: 10.12688/f1000research.21922.1 -
International Journal of Dermatology Mar 2023Woringer-Kolopp disease (WKD), also known as localized pagetoid reticulosis, is a rare variant of mycosis fungoides as described by the World Health... (Review)
Review
OBJECTIVE
Woringer-Kolopp disease (WKD), also known as localized pagetoid reticulosis, is a rare variant of mycosis fungoides as described by the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification system for cutaneous lymphomas. Our objective was to conduct a comprehensive review that describes and evaluates patient demographics, clinical presentation, immunohistochemical findings, management, and outcomes of WKD.
METHODS
The databases PubMed, Embase, and Cochrane Library were searched for relevant literature. Patient demographics, imaging, treatments, and other clinical characteristics were obtained. The literature search was conducted on December 7, 2020. Studies were included if they contained primary data related to WKD. Non-pertinent studies, non-English studies, non-human studies, review articles, or studies with insufficient case information were excluded. The quality of the included studies and the risk of bias were evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation Group (GRADE) criteria (2016), Oxford Centre for Evidence-Based Medicine: Levels of Evidence (OCEBM) (March 2009), and the Methodological Index for Non-Randomized Studies (MINORS) criteria (2003).
RESULTS
A total of 84 studies with 143 patients met the inclusion criteria for this study. The most common chief complaint was an asymptomatic, slow-growing, and erythematous plaque. The average time from initial skin eruption to presentation was 97.6 months. Histologically, 128 cases of WKD displayed epidermotropism (97.7%). Various therapies, including radiotherapy, surgery, and local chemotherapy, were used. In total, 92 (78.6%) cases had complete remission and 11 (9.4%) cases recurred.
CONCLUSIONS
WKD is a rare cutaneous T-cell lymphoma that often presents as a single plaque on the extremities with an indolent course and a favorable prognosis. However, it is often misdiagnosed, leading to delays in treatment. The diagnosis of WKD involves clinical appraisal, a biopsy of suspicious lesions, and immunohistochemistry. Monotherapy appears to be preferred compared to combination therapy for WKD with radiotherapy demonstrating among the highest cure rates and lowest recurrence. Future retrospective and prospective studies are needed to accurately determine the epidemiology, prognosis, and effective treatments for WKD. Limitations include a possibility of missed studies, heterogeneity in reporting methods, publication, and selection bias.
Topics: Humans; Pagetoid Reticulosis; Retrospective Studies; Mycosis Fungoides; Skin Neoplasms; Lymphoma, T-Cell, Cutaneous
PubMed: 35485962
DOI: 10.1111/ijd.16224